4-(4-{2-[(2-phenyl-5-trifluoromethyloxazole-4-carbonyl)amino]ethylcarbamoyl}phenoxy)adamantane-1-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(4-{2-[(2-phenyl-5-trifluoromethyloxazole-4-carbonyl)amino]ethylcarbamoyl}phenoxy)adamantane-1-carboxylic acid
• 英文别名: 4-[4-[2-[[2-Phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]ethylcarbamoyl]phenoxy]adamantane-1-carboxylic acid；4-[4-[2-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]ethylcarbamoyl]phenoxy]adamantane-1-carboxylic acid
• 化学式: C₃₁H₃₀F₃N₃O₆
• 分子量: 597.591
• InChiKey: WOLIBVYALKJNTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  43
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  131
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  对羟基苯甲酸苄酯 在 偶氮二甲酸二异丙酯 、 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三苯基膦 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 66.0h， 生成 4-(4-{2-[(2-phenyl-5-trifluoromethyloxazole-4-carbonyl)amino]ethylcarbamoyl}phenoxy)adamantane-1-carboxylic acid
  参考文献：
  名称：

  Discovery and optimization of adamantane carboxylic acid derivatives as potent diacylglycerol acyltransferase 1 inhibitors for the potential treatment of obesity and diabetes

  摘要：

  We have developed a series of adamantane carboxylic acid derivatives exhibiting potent diacylglycerol acyltransferase 1 (DGAT1) inhibitory activities. Optimization of the series led to the discovery of E-adamantane carboxylic acid compound 43c, which showed excellent in vitro activity with an IC50 value of 5 nM against human and mouse DGAT1, also good druggability as well as microsomal stability and safety profiles such as hERG, CYP and cytotoxicity. Compound 43c significantly reduced plasma triglyceride levels in vivo (in rodents and zebrafish) and also showed bodyweight gain reduction and glucose area under curve (AUC) lowering efficacy in diet-induced obesity (DIO) mice.[GRAPHICS](C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.06.043

文献信息

• Discovery and optimization of adamantane carboxylic acid derivatives as potent diacylglycerol acyltransferase 1 inhibitors for the potential treatment of obesity and diabetes
  作者：Suvarna H. Pagire、Haushabhau S. Pagire、Gwi Bin Lee、Seo-Jung Han、Hyun Jung Kwak、Ji Young Kim、Ki Young Kim、Sang Dal Rhee、Jeong Im Ryu、Jin Sook Song、Myung Ae Bae、Mi-jin Park、Dooseop Kim、Duck Hyung Lee、Jin Hee Ahn

  DOI：10.1016/j.ejmech.2015.06.043

  日期：2015.8

  We have developed a series of adamantane carboxylic acid derivatives exhibiting potent diacylglycerol acyltransferase 1 (DGAT1) inhibitory activities. Optimization of the series led to the discovery of E-adamantane carboxylic acid compound 43c, which showed excellent in vitro activity with an IC50 value of 5 nM against human and mouse DGAT1, also good druggability as well as microsomal stability and safety profiles such as hERG, CYP and cytotoxicity. Compound 43c significantly reduced plasma triglyceride levels in vivo (in rodents and zebrafish) and also showed bodyweight gain reduction and glucose area under curve (AUC) lowering efficacy in diet-induced obesity (DIO) mice.[GRAPHICS](C) 2015 Elsevier Masson SAS. All rights reserved.